Lin X, Huebner V
Chiron Corporation, Small Molecule Drug Discovery, Emeryville, CA 94608, USA.
Curr Opin Drug Discov Devel. 2000 Jul;3(4):383-98.
Nuclear hormone receptors play important roles in many physiological events. Small molecules, ie, ligands, can regulate these physiological effects by binding to the receptors forming a ligand-receptor complex, which in turn triggers a cascade of transcriptional events. Over the years, non-steroidal ligands for steroid receptors have been developed and have found extensive clinical use in cancer treatment, fertility regulation and hormone replacement therapy. This review summarizes the recent progress in the identification of pharmacologically relevant non-steroidal ligands for steroid receptors, focusing on the estrogen receptor (ER), the progesterone receptor (PR) and the androgen receptor (AR). The ligands are selected for discussion based on their clinical status, pharmacological profile and structural novelty, and range from compounds launched extensively to those in the early discovery stage.
核激素受体在许多生理过程中发挥着重要作用。小分子，即配体，可通过与受体结合形成配体-受体复合物来调节这些生理效应，进而引发一系列转录事件。多年来，已开发出用于类固醇受体的非甾体配体，并在癌症治疗、生育调节和激素替代疗法中得到广泛临床应用。本综述总结了在鉴定与类固醇受体具有药理学相关性的非甾体配体方面的最新进展，重点关注雌激素受体（ER）、孕激素受体（PR）和雄激素受体（AR）。根据其临床状态、药理学特征和结构新颖性选择这些配体进行讨论，范围从已广泛上市的化合物到处于早期发现阶段的化合物。
